Dermatophytoses is a disease caused by a group of fungi known as dermatophytes. It is also known as ringworm or tinea and involves superficial infection of keratinized tissue of the skin of animals and human beings. Various species of three anamorpohic (asexual or imperfect) genera Epidermophyton, Microsporum and Trichophyton are commonly involved in these mycoses. The disease is prominent in tropical and subtropical countries due to their prevailing moisture and temperature regimes, and poses a therapeutic problem despite several antimycotic drugs available in the market.
Treatment of dermatophytoses is by use of topical or oral antifungal agents. There are 17 synthetic chemical compounds which are generally utilized (Majumdar 1999 Indian drugs 36(1): 1-14) for various superficial fungal infections but many of them produce adverse effect with fungistatic action only. Since herbal medicines have been reported to be comparatively safe and without any adverse side effect there has been revival of interest in the use of medicinal plants in developed and developing countries.
During the course of research, in an attempt prepare fungitoxic formulation from natural products the applicants have found that volatile oil of Rabdosia melissodies can be employed for controlling a number of dermatophytes.
The plant Rabdosia melissodies Benth. Syn. Plactranthus melissoides (Lamiaceae) is an important source of thymol. For the first time this species was introduced for cultivation by Central Institute of Medicinal and Aromatic Plants (Singh et al. PAFAI Journal, January March, 67-69, 1986). It is an herbaceous plant found to grow scattered in nature especially in Tarai region of Uttar Pradesh, India. The leaves and inflorescence of the plant on hydrodistillation yield essential oil which has been reported to exhibit repellent and fumigant properties for storage grain insects (Singh & Singh 1991, Insect Science Application 12(4) 487-491.
The basis on which the invention has been developed is the applicant's own finding that the essential oil of Rabdosia melissoides acts as a potent antidermatophytic agent. The oil showed broad range of antifungal activity completely inhibiting the mycelial growth of fungi such as Microsporum abudouiniis, M. nanum, Trichophyton mentagrophytes var interdigitale, T. mentagrophytes var mentagraphytes, T. tonsurans, T. violaceum, Epidermophyton onvious floccosum, Microsporum gypseum and Trichophyton rubrum, considered to be the most important dermatophytes (Mehrotra et al 1978, Ind. J. Pathol. Microbiol 21: 131-134; Banerjee Pasricha 1987, Ind. J. Med. Microbiol, 5: 207-212).
Twelve constituents have been identified in the essential oil of leaves of Rabdosia melissoides [Singh et al 1983, Planta Medica 47(4) 256]. They are .varies.-pinene, camphene, .beta.-pinene, myrcene, .varies.-phellandrene, d-limonine, carene, .varies.-terpinene, p-cymene (25.4%), T-terpinene, thymol (19.8%) and carvacrol (15.4%). Thus thymol, p-cymene and carvacrol are the major constituents of the oil. There are quite a number of other plants viz. Origanum vulgare, O. majorana, Thymus serpyllum, Thymus vulgaris and Trachyspermum ammi syn Carum copticum Satureja montana and some Ocimum sp. which have been reported to contain thymol as a major constituent along with p-cymene and carvacrol. Among the oils of above plants, the oil of Origanum vulgare sp. hirtum has been reported to exhibit antifungal properties in vitro against human pathogens Malassezai furfur (yeast), Trichophyton rubrum (contains ginalool also) and Trichosporum beigelli [Konstantia et al 1998 J. Agric. Food. Chen. 46(5) 1739-1745). The oil showed promising results when tested on T. rubrum infected rats. The oil of Trachyspermum ammi contains 3 major constituents, thymol, carvacrol, and p-cymene, and has been reported to check growth of Epidermophyton floccosum, Microsporum canis, Trichophyton mentagrophytes in vitro. [Sing et al 1986; MyKosen 29(1) 37-40]. The oil of T. ammi has also been evaluated in the form of an ointment in human beings but it has been found to produce some adverse effects on the mammalian skin when applied locally. (Dixit et al. 1994 Traditional Medicinal Plants in Skin care CIMAP Publication, Lucknow, India p 12). The oils of Thymus serphyllum and T. vulgaris are reported to check the growth of Candida albicans. [Menghini et al 1987, Plantes Medicinales et Phytotherapie 21(1) 36-42].
Thymol, carvacrol and p-cymene have been reported to exhibit fungicidal activity (CRC Hand book of Medicinal Mints (Aromathematics) Phytochemicals and Biological activity, Stephen M. Beckstrom--Sternberg James A. Duke, CRC Press 1996 Printed in USA pp 419, 386, 409]. On further detailed literature survey it was found that thymol exhibits antifungal activity in vitro [Myers 1927, J. Am. Med Asso. 89 1834] and is effective as antifungal preservative [Dersarkission and Goodberry 1980, Studies Conserv 25-28] and checks the growth of honey bees pathogens, [Calderone et al. 1994, Journal of Essential Oil Research 6(3) 279-287]. p-Cymene has been found to check the growth of wood-habiting fungi Trichoderma viridi (De Groot 1972, Mycologia 64 862-870). While the carvacrol has been found to inhibit the germination and growth of vegetable post harvest pathogenic fungi (Caccioni et al 1994, Journal of Essential Oil Research 6(2) 173-179]. The essentials oil of Kunzea ericoides var. liniaris containing 31% p-cymene has weak antifungal activity (Perry et al 1997. Phytochem 45 (8) 1605-16012) which reveal that p-cymene is not useful for dermatophytoses and carvacrol up to 40% present in the oil of Saturega montana was found to inhibit the growth of only one species of Trichophyton and the nature of toxicity is also fungistatic (Menphini et al 1993 Riv. Ital FPOS, 4, SP. No. 566-71) for dermatophytoses further the Satureja montana oil was effective in 24-48 hour in 0.1 u ml/l while the oil of Rabdosia melissoides is effective in 80 minutes at the same concentration. The studies have shown the superiority of Rabdosia melissoides oil over thymol (Table 6).
So, it is very clear that p-cymene, carvacrol or thymol are not shown to be a good agent against dermatophytic fungi separately or in combinations present in various known oils but the combination of these, present in R. melissoides oil along with certain unidentified constituents played a synergistic fungicidal action, so the oil from the plant--R. melissoides is a potential novel source for cure of dermatophytoses and its formulation development is also a novelty.
Thus available information about the essential oils and plants having thymol, carvacrol and p-cymene as major constituents or in isolation have not been found to act as antifungal agents effective against a broad spectrum of cutaneous mycoses/dermatophytoses.